Chapter 13 - Hematology Flashcards
1
Q
Describe qualitative and quantitative changes in hemoglobin during infancy.
A
- hemoglobin is high at birth and then declines
- in term infants, it reaches a nadir around 2-3 months of age; in preterm infants, it reaches a nadir after 1-2 months of age
- after birth, HbF is gradually replaced by HbA and disappears by 6-9 months of age
2
Q
What is a normal reticulocyte count, how is the corrected reticulocyte count determined, what constitutes an appropriate response to anemia?
A
- normal is 1%
- corrected by taking RC x Hct/45
- 3% corrected is an appropriate response to anemia
3
Q
What are five diseases that result in a microcytic anemia?
A
- iron deficiency
- thalassemia
- sideroblastic anemia
- lead toxicity
- chronic disease
4
Q
Iron Deficiency Anemia
A
- a microcytic anemia caused by inadequate iron intake or occult blood loss
- nutritional deficiency is more common in those 9-24 months and in adolescent girls whereas occult blood loss is indicative of polyps, Meckle’s, IBD, ulcers, etc.
- presents with the signs and symptoms of anemia plus koilonychia and pica
- labs: low ferritin, high TIBC, low % saturation, low serum iron, elevated erythrocyte protoporphyrin, increased RDW
- treated with ferrous sulfate and vitamin C to enhance intestinal iron absorption; transfusion may be required for severe cases
5
Q
a-Thalassemia
A
- deletion of one or more alpha genes on chromosome 16
- 1: asymptomatic
- 2: mild anemia with the cis form more common amongst Asians and the trans more common in Africans
- 3: HbH (B4) disease with severe anemia at birth
- 4: HbBarts (y4) with congestive heart failure and hydrops fetalis
6
Q
B-Thalassemia Minor
A
- a mutation of one of the beta genes on chromosome 11
- most common in Mediterraneans and Africans
- largely asymptomatic but may present as a microcytic anemia with target cells and slightly elevated HbA2 and HbF
7
Q
B-Thalassemia Major
A
- a mutation of two of the beta genes on chromosome 11
- unpaired alpha chains precipitate and damage RBC membranes, contributing to ineffective hematopoiesis and extravascular hemolysis
- massive erythropoiesis ensues with hepatosplenomegaly, crewcut sign, and chipmunk facies
- labs find a severe microcytic anemia, target cells, elevated HbF, elevated UCB, and elevated LDH
- requires lifelong transfusions and often splenectomy
- hemochromatosis and risk of aplastic crisis are the major complications
8
Q
Sideroblastic Anemia
A
- a microcytic anemia due to defective protoporphyrin synthesis
- most commonly caused by an X-linked deficiency of ALA synthase, which converts succinyl-CoA and glycine to ALA
- other causes include lead poisoning, which inhibits ALAD and ferrochelatase; and VitB6 deficiency, secondary to isoniazid treatment, which is a required ALAS cofactor
- iron-laden mitochondria form a ring around the nucleus, which are then called ringed-sideroblasts
- ferritin is high, TIBC is low, serum iron is high, and % saturation is high (all opposite IDA, consistent with iron overload)
9
Q
What are ringed sideroblasts?
A
pathologic RBCs found in those with sideroblastic anemia and formed via the excess accumulation of iron in mitochondria
10
Q
Lead Poisoning
A
- lead inhibits ferrochelatase and ALA dehydratase, enzymes needed for heme synthesis
- ALA and protoporphyrin accumulate in the blood
- presents with a microcytic, sideroblastic anemia with basophilic stippling, GI and kidney disease
- causes mental deterioration in children (most likely from exposure to lead paint)
- causes headache, memory loss, and demyelination in adults (most likely from exposure to batteries or ammunition)
11
Q
All megaloblastic anemias have what in common?
A
- impaired DNA synthesis
- presenting with a macrocytic anemia, hyper-segmented neutrophils, and glossitis
12
Q
Folate Deficiency Anemia
A
- a megaloblastic, macrocytic anemia characterized by impaired synthesis of DNA precursors
- caused by poor diet, increased demand, or use of folate antagonists such as methotrexate
- body stores are minimal so deficiency can occur quickly
- presents with a macrocytic anemia, hyper-segmented neutrophils, glossitis, increased homocysteine, and normal methylmalonic acid
13
Q
B12 Deficiency Anemia
A
- a megaloblastic, macrocytic anemia
- most often due to pernicious anemia, pancreatic insufficiency, damage to the terminal ileum (Crohn disease or Diphyllobothrium datum), or veganism
- takes a long time to develop since hepatic stores are large
- presents with hyper-segmented neutrophils, glossitis, and demyelination of the spinal cord contributing to poor proprioception, impaired vibratory sensation, and spastic paresis
- labs reveal elevated homocysteine and methylmalonic acid
- treat with money IM vitamin B12 injections
14
Q
How can folate deficiency anemia be differentiated from B12 deficiency anemia?
A
- B12 is accompanied by neurologic symptoms
- B12 is characterized by elevated methylmalonic acid while levels are normal in those with a folate deficiency
15
Q
Describe how B12 is absorbed.
A
- salivary gland enzymes liberate it
- it is then bound by R-binder and carried through the stomach
- pancreatic proteases in the duodenum detach it from R-binder
- it is then bound by intrinsic factor from gastric parietal cells and the complex is absorbed in the ileum
16
Q
Hereditary Spherocytosis
A
- an autosomal dominant defect or deficiency of spectrin, a cytoskeleton-membrane tethering proteins
- this leads to blebs of membrane being lost over time, rending cells round
- those spherocytes are unable to navigate splenic sinusoids and are cleared, resulting in anemia
- RDW and MCHC are elevated since cells get smaller with each bleb that is lost but don’t lose hemoglobin
- presents like other extravascular hemolytic anemias (splenomegaly, pigmented gallstones, jaundice) and an increased risk for aplastic crisis
- diagnosed via elevated reticulocyte count, hyperbilirubinemia, and an osmotic fragility test in which cells are placed in a hypotonic solution
- treat with transfusions until age 5 when splenectomy can be performed with lower risk for severe infection
17
Q
Hereditary Elliptocytosis
A
- an autosomal dominant defect in the structure of spectrin
- most cases are asymptomatic but presentation may include normocytic anemia, jaundice, splenomegaly, and gallstones
- elliptical RBCs are found on blood smear
- splenectomy is used to treat symptomatic patients
18
Q
G6PDH Deficiency
A
- an X-linked recessive defect that limits production of NADPH and thus glutathione, needed for neutralization of reactive oxygen species
- this leaves cells susceptible to oxidative stress and intravascular hemolysis; usually induced by infection, primaquine, sulfa drugs, dapsone, or fava beans
- presents with hemoglobinuria and back pain hours after exposure; Heinz bodies and bite cells can be seen on a blood smear
- enzyme studies are performed weeks after a hemolytic episode because during the episode, G6PDH-deficient cells are all lysed
19
Q
What are bite cells and how are they formed?
A
bite cells are a feature of G6PD deficiency which from when oxidative stress precipitates hemoglobin, forming Heinz bodies which are then removed by splenic macrophages leaving bite cells
20
Q
What are Heinz bodies? What disease are they associated with? How are they formed? What do they lead to?
A
- a feature of G6PD deficiency
- form when oxidative stress precipitates hemoglobin (by forming sulfide bonds)
- likely removed by the spleen to form bite cells
21
Q
What are Howell-Jolly bodies? When are they seen?
A
they are basophilic nuclear remnants found in RBCs that are normally removed by splenic macrophages but are seen in patients with asplenia or splenic dysfunction
22
Q
Basophilic stippling of RBCs is indicative of what three pathologies?
A
- lead poisoning
- sideroblastic anemia (defect in porphyrin metabolism)
- myelodysplastic syndromes
23
Q
Autoimmune Hemolytic Anemia
A
- occurs when antibodies are misdirected against RBCs
- may be idiopathic or associated with an underlying disease process (SLE, lymphoma, immunodeficiency)
- classified as fulminant acute type, which presents as acute onset pallor, jaundice, hemoglobinuria, and splenomegaly in infants and younger children after a respiratory infection; recovery is expected
- or as the prolonged type which has a protracted course and high mortality
- labs find severe normocytic anemia, spherocytes, prominent reticulocytosis, leukocytosis, and a positive direct Coombs test
- treated with transfusions and steroids until hemolysis diminishes
24
Q
Rh Hemolytic Disease
A
- Rhd mothers exposed to fetal RhD blood (often during delivery) make anti-D IgG
- in subsequent pregnancies this IgG crosses the placenta, causing erythroblastosis fetalis
- presents with severe jaundice, anemia, hepatosplenomegly, hydrops fetalis, and a strongly positive direct Coombs test
- prevented by administration of RhoGAM to Rhd pregnant women during the third trimester
25
Q
ABO Hemolytic Disease
A
- anti-A or anti-B IgG from type O mothers crosses the placenta, attacking the fetal erythrocytes
- these antibodies are preformed so it can occur in the first pregnancy and does not worsen in future pregnancies
- presents with mild jaundice in the neonate within 24 hours of birth
- labs find a weakly positive direct Coombs test
- treat with phototherapy
